Mechanisms of Metal-Induced Hepatic Inflammation.

Purpose Of Review: Worldwide, there is an increasing prevalence of hepatic diseases. The most common diseases include alcoholic-associated liver disease (ALD), metabolic dysfunction-associated fatty liver disease/ metabolic dysfunction-associated steatohepatitis (MAFLD/MASH) and viral hepatitis. While there are many important mediators of these diseases, there is increasing recognition of the importance of the inflammatory immune response in hepatic disease pathogenesis.

Sex-specific alterations in pulmonary metabolic, xenobiotic and lipid signalling pathways after e-cigarette aerosol exposure during adolescence in mice.

Background: E-cigarette use is now prevalent among adolescents and young adults, raising concerns over potential adverse long-term health effects. Although it is hypothesised that e-cigarettes promote inflammation, studies have yielded conflicting evidence. Our previous work showed that JUUL, a popular e-cigarette brand, elicited minimal lung inflammation but induced significant molecular changes in adult C57BL/6 mice.

Chronic exposure to E-cigarette aerosols potentiates atherosclerosis in a sex-dependent manner.

Despite being designed for smoking cessation, e-cigarettes and their variety of flavors have become increasingly attractive to teens and young adults. This trend has fueled concerns regarding the potential role of e-cigarettes in advancing chronic diseases, notably those affecting the cardiovascular system. E-cigarettes contain a mixture of metals and chemical compounds, some of which have been implicated in cardiovascular diseases like atherosclerosis.

Phenotypic and Functional Outcomes in Macrophages Exposed to an Environmentally Relevant Mixture of Organophosphate Esters .

Background: Organophosphate esters (OPEs) are flame retardants and plasticizers used in consumer products. OPEs are found ubiquitously throughout the environment with high concentrations in indoor house dust. Exposure to individual OPEs is associated with immune dysfunction, particularly in macrophages.

scCross: a deep generative model for unifying single-cell multi-omics with seamless integration, cross-modal generation, and in silico exploration.

Single-cell multi-omics data reveal complex cellular states, providing significant insights into cellular dynamics and disease. Yet, integration of multi-omics data presents challenges. Some modalities have not reached the robustness or clarity of established transcriptomics.

Dietary Minerals and Incident Cardiovascular Outcomes among Never-Smokers in a Danish Case-Cohort Study.

Diet is known to impact cardiovascular disease (CVD) risk, but evidence for the essential minerals of magnesium (Mg), calcium (Ca), and potassium (K) is inconsistent. We conducted a case-cohort study within a non-smoking subgroup of the Danish Diet, Cancer and Health cohort, a prospective study of 50-64-year-olds recruited between 1993-1997. We identified incident heart failure (HF), acute myocardial infarction (AMI) and stroke cases through 2015 with an 1135-member subcohort.

The 11 Conference on metal toxicity and carcinogenesis.

Metal exposure is linked to numerous pathological outcomes including cancer, cardiovascular disease, and diabetes. Over the past decades, we have made significant progress in our understanding of how metals are linked to disease, but there is still much to learn. In October 2022, experts studying the consequences of metal exposures met in Montréal, Québec, to discuss recent advances and knowledge gaps for future research.

Tunable PhenoCycler imaging of the murine pre-clinical tumour microenvironments.

Background: The tumour microenvironment (TME) consists of tumour-supportive immune cells, endothelial cells, and fibroblasts. PhenoCycler, a high-plex single cell spatial biology imaging platform, is used to characterize the complexity of the TME. Researchers worldwide harvest and bank tissues from mouse models which are employed to model a plethora of human disease.

E-cigarette exposure causes early pro-atherogenic changes in an inducible murine model of atherosclerosis.

Evidence suggests that e-cigarette use (vaping) increases cardiovascular disease risk, but decades are needed before people who vape would develop pathology. Thus, murine models of atherosclerosis can be utilized as tools to understand disease susceptibility, risk and pathogenesis. Moreover, there is a poor understanding of how risk factors for atherosclerosis (i.

Maternal exposure to pyrethroid insecticides during pregnancy and respiratory allergy symptoms among children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE).

Background: Pyrethroid insecticides use for indoor residual spraying (IRS) in malaria-endemic areas results in high levels of exposure to local populations. Pyrethroids may cause asthma and respiratory allergies but no prior study has investigated this question in an IRS area.

Methods: We measured maternal urinary concentrations of pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA) in samples collected at delivery from 751 mothers participating in the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE), a birth cohort study based in Limpopo, South Africa.

In vitro and in vivo approaches to assess atherosclerosis following exposure to low-dose mixtures of arsenic and cadmium.

Worldwide, millions of people are co-exposed to arsenic and cadmium. Environmental exposure to both metals is linked with a higher risk of atherosclerosis. While studies have characterized the pro-atherosclerotic effects of arsenic and cadmium as single agents, little is known about the potential effects of metal mixtures, particularly at low doses.

Contaminant Metals as Cardiovascular Risk Factors: A Scientific Statement From the American Heart Association.

Exposure to environmental pollutants is linked to increased risk of cardiovascular disease. Beyond the extensive evidence for particulate air pollution, accumulating evidence supports that exposure to nonessential metals such as lead, cadmium, and arsenic is a significant contributor to cardiovascular disease worldwide. Humans are exposed to metals through air, water, soil, and food and extensive industrial and public use.

B cell-specific knockout of AID protects against atherosclerosis.

Antigen-naive IgM-producing B cells are atheroprotective, whereas mature B cells producing class-switched antibodies promote atherosclerosis. Activation-induced cytidine deaminase (AID), which mediates class switch recombination (CSR), would thus be expected to foster atherosclerosis. Yet, AID also plays a major role in the establishment of B cell tolerance.

Chronic low-level JUUL aerosol exposure causes pulmonary immunologic, transcriptomic, and proteomic changes.

E-cigarettes currently divide public opinion, with some considering them a useful tool for smoking cessation and while others are concerned with potentially adverse health consequences. However, it may take decades to fully understand the effects of e-cigarette use in humans given their relative newness on the market. This highlights the need for comprehensive preclinical studies investigating the effects of e-cigarette exposure on health outcomes.

Arsenic causes distinct gene expression changes in macrophages polarized in vitro with either interferon-γ or interleukin-4.

Arsenic exposure is correlated with atherosclerosis in epidemiological studies and in animal models. We have previously shown that arsenic exposure enhanced the atherosclerotic plaque size, increased the plaque lipid content, and decreased the plaque smooth muscle cell and collagen contents in the apolipoprotein E knockout (apoE-/-) mice. However, the percentage of plaque-resident macrophages, the primary drivers of atherosclerosis remained unchanged.

Analyzing the Tumor-Immune Microenvironment by Flow Cytometry.

Flow cytometry is an essential tool for studying the tumor-immune microenvironment. It allows us to quickly quantify and identify multiple cell types in a heterogeneous sample. This chapter provides an overview of the flow cytometry instrumentation and a discussion of the appropriate considerations and steps in building a reproducible flow cytometry staining panel.

Arsenic as an immunotoxicant.

Arsenic is world-wide contaminant to which millions of people are exposed. The health consequences of arsenic exposure are varied, including cancer, cardiometabolic disease, and respiratory disorders. Arsenic is also toxic to the immune system, which may link many of the pathologies associated with arsenic exposure.

Overview of the cardiovascular effects of environmental metals: New preclinical and clinical insights.

Environmental causes of cardiovascular diseases (CVDs) are global health issues. In particular, an association between metal exposure and CVDs has become evident but causal evidence still lacks. Therefore, this symposium at the Society of Toxicology 2022 annual meeting addressed epidemiological, clinical, pre-clinical animal model-derived and mechanism-based evidence by five presentations: 1) An epidemiologic study on potential CVD risks of individuals exposed occupationally and environmentally to heavy metals; 2) Both presentations of the second and third were clinical studies focusing on the potential link between heavy metals and pulmonary arterial hypertension (PAH), by presenting altered blood metal concentrations of both non-essential and essential metals in the patients with PAH and potential therapeutic approaches; 3) Arsenic-induced atherosclerosis via inflammatory cells in mouse model; 4) Pathogenic effects on the heart by adult chronic exposure to very low-dose cadmium via epigenetic mechanisms and whole life exposure to low dose cadmium via exacerbating high-fat-diet-lipotoxicity.

Quantification of local zinc and tungsten deposits in bone with LA-ICP-MS using novel hydroxyapatite-collagen calibration standards.

Tungsten has recently emerged as a potential toxicant and is known to heterogeneously deposit in bone as reactive polytungstates. Zinc, which accumulates in regions of bone remodeling, also has a heterogenous distribution in bone. Determining the local concentrations of these metals will provide valuable information about their mechanisms of uptake and action.

Arsenic Exposure, Blood DNA Methylation, and Cardiovascular Disease.

Background: Epigenetic dysregulation has been proposed as a key mechanism for arsenic-related cardiovascular disease (CVD). We evaluated differentially methylated positions (DMPs) as potential mediators on the association between arsenic and CVD.

Methods: Blood DNA methylation was measured in 2321 participants (mean age 56.

Differential impact of JUUL flavors on pulmonary immune modulation and oxidative stress responses in male and female mice.

JUUL is a popular e-cigarette brand that manufactures e-liquids in a variety of flavors, such as mango and mint. Despite their popularity, the pulmonary effects of flavored JUUL e-liquids that are aerosolized and subsequently inhaled are not known. Therefore, the purpose of this study was to evaluate if acute exposure to JUUL e-cigarette aerosols in three popular flavors elicits an immunomodulatory or oxidative stress response in mice.

Arsenic 3 methyltransferase (AS3MT) automethylates on cysteine residues in vitro.

Arsenic toxicity is a global concern to human health causing increased incidences of cancer, bronchopulmonary, and cardiovascular diseases. In human and mouse, inorganic arsenic (iAs) is metabolized in a series of methylation steps catalyzed by arsenic (3) methyltransferase (AS3MT), forming methylated arsenite (MAsIII), dimethylarsenite (DMAIII) and the volatile trimethylarsine (TMA). The methylation of arsenic is coordinated by four conserved cysteines proposed to participate in catalysis, namely C33, C62, C157, and C207 in mouse AS3MT.

Loss of NFE2L3 protects against inflammation-induced colorectal cancer through modulation of the tumor microenvironment.

We investigated the role of the NFE2L3 transcription factor in inflammation-induced colorectal cancer. Our studies revealed that Nfe2l3 mice exhibit significantly less inflammation in the colon, reduced tumor size and numbers, and skewed localization of tumors with a more pronounced decrease of tumors in the distal colon. CIBERSORT analysis of RNA-seq data from normal and tumor tissue predicted a reduction in mast cells in Nfe2l3 animals, which was confirmed by toluidine blue staining.

Acquired Resistance to EZH2 Inhibitor GSK343 Promotes the Differentiation of Human DLBCL Cell Lines toward an ABC-Like Phenotype.

Diffuse large B-cell lymphoma (DLBCL) accounts for 40% of non-Hodgkin lymphoma, and 30% to 40% of patients will succumb to relapsed/refractory disease (rrDLBCL). Patients with rrDLBCL generally have low long-term survival rates due to a lack of efficient salvage therapies. Small-molecule inhibitors targeting the histone methyltransferase EZH2 represent an emerging group of novel therapeutics that show promising clinical efficacy in patients with rrDLBCL.